One of intriguing features of mesangial cells (MCs) is their extraordinary abundance in gap junctions (GJs). However, information about the functional role of GJs in glomerular cells is still lacking. Our studies were designed to address this question. Our findings can be summarized as followings. 1. MCs are coupled by functional GJ channels. MCs were demonstrated to express GJ protein Cx43 and exhibited functional GJIC as assessed by dye-transfer assay. 2. GJ mediates the transmission of intercellular signal. Mechanical stimulation of a single MC initiated a rise in Ca^<2+> in the stimulated cells, which was followed by transmission of the signal to surrounding cells. The spreading of the Ca^<2+> signal in MCs was completely prevented by GJ inhibitors. 3. Regulation of MC phenotypes by glomerular endothelial cells via GJs. Using cultured human glomerular cells, endothelial cells were demonstrated to express GJ proteins including Cx43, Cx40 and Cx37, and GJ, which was functional, as as
… Moresessed by dye-transfer assay. Ultrastructural study revealed that presence of GJ protein Cx43 between endothelial cells and MCs. GJ might participates in the endothelial-mediated regulation of MC functions. 4. Regulation of GJ by endothelial-derived vasodilative factor nitric oxide (NO). Endothelial derived vasodiative factor, nitric oxide (NO), was identified to be a potent stimulator of Cx43 expression and functional gap junctional intercellular communication (GJIC) in MCs. This action of NO was shown to be due to the activation of protein kinase A via cGMP-dependent inhibition of phosphodiesterase 3 (PDE3). This finding may open a new window toward our further understanding of the vascular role of NO under various pathophysiologic situations. In conclusion, several lines of evidence support the important roles of GJs in MC functions. (1) MCs are extensively connected by functional GJs. (2) GJs in MCs participate in the regulation of important physiological processes, including tubuloglomerular feedback and glomerular filtration. (3) Factors critically involved in various processes of glomerular pathophysiology are potent regulators of Cx43 expression and GJIC in MCs. These data suggest that GJs may participate in glomerular pathophysiology. Less